Methods have been described for enhancing skin permeation of drugs by using a device that gradually eases microneedles into contact with the skin, for example by forming an array of microneedles directly on a roller or, as described in international patent application WO 2008/125798, by forming an array of microneedles on a patch secured to a belt that travels over a set of rollers. This method has been demonstrated to be superior to simply pressing a flat array of microneedles against the skin. That is because less insertion force is required and because, given that the array of needles is inserted row by row, the reproducibility of the dose is also increased independently of the operator.
The main barrier to delivery of drugs through the skin is the stratum corneum, which is a tough outer layer of dead skin cells. The microneedles may be hollow to provide a channel for delivery of a fluid drug through the stratum corneum or they may be solid and simply coated with the drug for delivery. Alternatively, a device comprising solid microneedles may be used to disrupt the stratum corneum and/or to create pores through it in order to enhance its permeability to a drug that is subsequently applied to the surface of the skin, for example in the form of a gel or in a patch.
It has been proposed that the microneedles themselves may be produced from a formulation of the drug. On application to the skin of a patient, the needles break and remain in the skin, where the formulation dissolves and the active substance is absorbed into the blood stream. The formulation may be adapted to give rapid or slow release once the needles have been inserted into the skin. Such needles may be manufactured using metal insert moulds that are laser etched to give high tolerance features and good reproducibility. The mechanical properties of the needles must be such that the needles do not break during their formation, storage or transport, yet they should easily break off upon insertion into the skin. Furthermore the arrays of needles, which usually number hundreds to thousands of individual microneedles, must be mass-produced in a consistent manner for consistent dosing. The micro-manufacture of such moulds for known microneedle arrays is a slow and expensive process. The resulting arrays of microneedles are limited in size.
A further route for delivery of a drug into the body of a patient, especially for treatment of optical disorders, is through the surface of the cornea of the eye. For the purposes of this specification, that route is included within the term “transdermal”.